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. 1987 Aug 25;15(16):6713–6731. doi: 10.1093/nar/15.16.6713

DNA unwinding and inhibition of mouse leukemia L1210 DNA topoisomerase I by intercalators.

Y Pommier, J M Covey, D Kerrigan, J Markovits, R Pham
PMCID: PMC306134  PMID: 2819825

Abstract

The DNA unwinding effects of some 9-aminoacridine derivatives were compared under reaction conditions that could be used to study drug-induced topoisomerase II inhibition. An assay was designed to determine drug-induced DNA unwinding by using L1210 topoisomerase I. 9-aminoacridines could be ranked by decreasing unwinding potency: compound C greater than or equal to 9-aminoacridine greater than o-AMSA greater than or equal to compound A greater than compound B greater than m-AMSA. Ethidium bromide was more potent than any of the 9-aminoacridines. This assay is a fast and simple method to compare DNA unwinding effects of intercalators. It led to the definition of a drug intrinsic unwinding constant (k). An additional finding was that all 9-aminoacridines and ethidium bromide inhibited L1210 topoisomerase I. Enzyme inhibition was detectable at low enzyme concentrations (less than or equal to 1 unit) and when the kinetics of topoisomerase I-mediated DNA relaxation was studied. Topoisomerase I inhibition was not associated with DNA swivelling or cleavage.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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